Compounds which possess structural features common to both enkephalin and exogenous ligands (benzomorphans, 4-phenylpiperidines, and fentanyl-type compounds) will be synthesized. The distinguishing feature of the target compounds is that they all are derivatives of pipecolic acid. The carbonyl-containing function in many of these derivatives is located at a position equivalent to that of C-9 hydrogen of morphine, which corresponds sterically to the peptide carbonyl group of enkephalin. The proposed series will consist of ester, amide, and peptide derivatives of the substituted pipecolic acids. Some of the peptides will be pentapeptide analogues of enkephalin. Groups which usually confer high agonist or opioid antagonist activity will be located in the target molecules in an effort to develop potent analgetics and narcotic antagonists. Additionally, the analogues will be employed to determine whether or not the same aromatic binding site on the receptor can accomodate either a phenolic or nonphenolic group. Still other studies will explore the role of peptide chain lengthening on antagonist activity. All of the target compounds will be evaluated in vitro and in vivo using established procedures.